Diagnosis and treatment of cancer expressing ILT3 or ILT3 ligand
The present invention relates to methods of using the expression of ILTL3 ligand or ILT3 on certain types of cancer cells as a diagnostic tool. Methods are provided for treating ILT3-ligand expressing cancers, such as T-cell acute lymphoblastic leukemia (T-cell acute lymphoblastic leukemia), for example by administering ILT3, the extracellular domain of ILT3 or ILT3Fc conjugated to a cytotoxic agent to kill the targeted cancer cell. Other methods are provided for treating cancers that express ILT3 on their surface, such as monocytic forms of AML, for example by administering anti-ILT3 antibodies conjugated to a cytotoxic agent.
1. A method of treating T-cell acute lymphoblastic leukemia comprising
(a) identifying a subject that has T-cell acute lymphoblastic leukemia;
(b) administering to the subject an amount of ILT3Fc, the extracellular domain of ILT3 or a fragment thereof comprising the ILT3 ligand binding site or combinations thereof, which ILT3Fc, extracellular domain and fragment is linked either to a radioactive isotope that emits radiation at a level that kills the leukemia cell or to a cytotoxic agent;
(c) obtaining a pre-treatment and a post-treatment biological test sample from the subject;
(d) contacting the samples with an ILT3 ligand-binding probe under conditions that permit the probe to bind to T-cell acute lymphoblastic leukemia cancer cells;
(e) determining the number of T-cell acute lymphoblastic leukemia cells that are bound to the probe in the pre and post treatment samples; and
(f) determining that the subject is responding to treatment if the number of T-cell acute lymphoblastic leukemia cells in the pre-treatment sample is significantly higher than the number of T-cell acute lymphoblastic leukemia cells in the posttreatment sample.
2. A method of treating an ILT3 ligand-expressing cancer comprising,
a) identifying a subject in need of treatment for a cancer that expresses ILT3 ligand on its surface, and
b) administering to the subject therapeutically effective amounts of ILT3Fc, the extracellular domain of ILT3 or a fragment thereof comprising the ILT3 ligand binding site or combinations thereof, which ILT3Fc, extracellular domain and fragment is linked either to a radioactive isotope that emits radiation at a level that kills the cancer cell or to a cytotoxic agent, thereby treating the subject for the ILT3 ligand-expressing cancer, wherein the cancer that expresses ILT3 ligand is T-cell acute lymphoblastic leukemia (T-ALL).
3. The method according to claim 2 , wherein the cytotoxic agent is a member selected from the group consisting of Taxol, Pseudomonas exotoxic fragment, cytocalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etopside, tenopside, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy antracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosteron, glycocorticoids, procain, tetracaine, lidokaine, propranolol, puromycin, and combinations thereof.